PubMed:24740633
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/24740633","sourcedb":"PubMed","sourceid":"24740633","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/24740633","text":"HIV-1 drug resistance in the iPrEx preexposure prophylaxis trial.\nBACKGROUND: The iPrEx study demonstrated that combination oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) as preexposure prophylaxis (PrEP) protects against HIV acquisition in men who have sex with men and transgender women. Selection for drug resistance could offset PrEP benefits.\nMETHODS: Phenotypic and genotypic clinical resistance assays characterized major drug resistant mutations. Minor variants with FTC/TDF mutations K65R, K70E, M184V/I were measured using 454 deep sequencing and a novel allele-specific polymerase chain reaction (AS-PCR) diagnostic tolerant to sequence heterogeneity.\nRESULTS: Control of primer-binding site heterogeneity resulted in improved accuracy of minor variant measurements by AS-PCR. Of the 48 on-study infections randomized to FTC/TDF, none showed FTC/TDF mutations by clinical assays despite detectable drug levels in 8 participants. Two randomized to FTC/TDF had minor variant M184I detected at 0.53% by AS-PCR or 0.75% by deep sequencing, only 1 of which had low but detectable drug levels. Among those with acute infection at randomization to FTC/TDF, M184V or I mutations that were predominant at seroconversion waned to background levels within 24 weeks after discontinuing drug.\nCONCLUSIONS: Drug resistance was rare in iPrEx on-study FTC/TDF-randomized seroconverters, and only as low-frequency minor variants. FTC resistance among those initiating PrEP with acute infection waned rapidly after drug discontinuation. Clinical Trials Registration.NCT00458393.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":182,"end":185},"obj":"gene:6736"},{"id":"T1","span":{"begin":238,"end":241},"obj":"disease:C0019693"},{"id":"T2","span":{"begin":1172,"end":1175},"obj":"gene:6736"},{"id":"T3","span":{"begin":1132,"end":1147},"obj":"disease:C0275518"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#93eccf","default":true}]}]}}